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PMID: 17158511 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Systematic variation in mRNA 3'-processing signals during mouse spermatogenesis.

Nucleic acids research ·Vol. 35 ·No. 1 ·2007-00-00 ·Pages 234-46

Liu D, Brockman JM, Dass B, Hutchins LN, Singh P, McCarrey JR, MacDonald CC, Graber JH

Abstract

Gene expression and processing during mouse male germ cell maturation (spermatogenesis) is highly specialized. Previous reports have suggested that there is a high incidence of alternative 3'-processing in male germ cell mRNAs, including reduced usage of the canonical polyadenylation signal, AAUAAA. We used EST libraries generated from mouse testicular cells to identify 3'-processing sites used at various stages of spermatogenesis (spermatogonia, spermatocytes and round spermatids) and testicular somatic Sertoli cells. We assessed differences in 3'-processing characteristics in the testicular samples, compared to control sets of widely used 3'-processing sites. Using a new method for comparison of degenerate regulatory elements between sequence samples, we identified significant changes in the use of putative 3'-processing regulatory sequence elements in all spermatogenic cell types. In addition, we observed a trend towards truncated 3'-untranslated regions (3'-UTRs), with the most significant differences apparent in round spermatids. In contrast, Sertoli cells displayed a much smaller trend towards 3'-UTR truncation and no significant difference in 3'-processing regulatory sequences. Finally, we identified a number of genes encoding mRNAs that were specifically subject to alternative 3'-processing during meiosis and postmeiotic development. Our results highlight developmental differences in polyadenylation site choice and in the elements that likely control them during spermatogenesis.

MeSH Terms
3' Untranslated Regions/chemistry Animals Evolution, Molecular Expressed Sequence Tags/chemistry Male Mice Polyadenylation RNA 3' Polyadenylation Signals RNA, Messenger/chemistry,metabolism Spermatogenesis/genetics Testis/metabolism mRNA Cleavage and Polyadenylation Factors/metabolism
Chemicals
3' Untranslated Regions RNA, Messenger mRNA Cleavage and Polyadenylation Factors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Liu Donglin
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Brockman J Michael
Dass Brinda
Hutchins Lucie N
Singh Priyam
McCarrey John R
MacDonald Clinton C
Graber Joel H
References (86)
86 references, click to expand
  1. An intronic polyadenylation site in human and mouse CstF-77 genes suggests an evolutionarily conserved regulatory mechanism.
    Gene. 2006 Feb 1;366(2):325-34 PMID: 16316725
  2. Quantitative comparison of EST libraries requires compensation for systematic biases in cDNA generation.
    BMC Bioinformatics. 2006;7:77 PMID: 16503995
  3. A multispecies comparison of the metazoan 3'-processing downstream elements and the CstF-64 RNA recognition motif.
    BMC Genomics. 2006;7:55 PMID: 16542450
  4. Secondary structure as a functional feature in the downstream region of mammalian polyadenylation signals.
    Mol Cell Biol. 2004 Apr;24(7):2789-96 PMID: 15024068
  5. Learning the parts of objects by non-negative matrix factorization.
    Nature. 1999 Oct 21;401(6755):788-91 PMID: 10548103
  6. In silico detection of control signals: mRNA 3'-end-processing sequences in diverse species.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14055-60 PMID: 10570197
  7. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  8. The 3' untranslated region of messenger RNA: A molecular 'hotspot' for pathology?
    Nat Med. 2000 Jun;6(6):637-41 PMID: 10835679
  9. Patterns of variant polyadenylation signal usage in human genes.
    Genome Res. 2000 Jul;10(7):1001-10 PMID: 10899149
  10. RNA processing and the control of spermatogenesis.
    Front Horm Res. 1999;25:34-58 PMID: 10941401
  11. An intronless gene encoding a poly(A) polymerase is specifically expressed in testis.
    FEBS Lett. 2000 Dec 29;487(2):287-92 PMID: 11150526
  12. hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells.
    Mol Cell Biol. 2001 Feb;21(4):1228-38 PMID: 11158309
  13. The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice.
    J Biol Chem. 2001 Mar 16;276(11):8044-50 PMID: 11113135
  14. Translational control by CPEB: a means to the end.
    Nat Rev Mol Cell Biol. 2001 Jul;2(7):521-9 PMID: 11433366
  15. Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data.
    Genome Res. 2001 Sep;11(9):1520-6 PMID: 11544195
  16. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  17. An extensive class of small RNAs in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):862-4 PMID: 11679672
  18. MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage.
    Biol Reprod. 2005 Sep;73(3):427-33 PMID: 15901636
  19. PACdb: PolyA Cleavage Site and 3'-UTR Database.
    Bioinformatics. 2005 Sep 15;21(18):3691-3 PMID: 16030070
  20. Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation.
    RNA. 2005 Oct;11(10):1485-93 PMID: 16131587
  21. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.
    Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 PMID: 16199517
  22. UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs. Update 2002.
    Nucleic Acids Res. 2002 Jan 1;30(1):335-40 PMID: 11752330
  23. A PUF family portrait: 3'UTR regulation as a way of life.
    Trends Genet. 2002 Mar;18(3):150-7 PMID: 11858839
  24. Mechanisms of subcellular mRNA localization.
    Cell. 2002 Feb 22;108(4):533-44 PMID: 11909524
  25. BLAT--the BLAST-like alignment tool.
    Genome Res. 2002 Apr;12(4):656-64 PMID: 11932250
  26. Downstream sequence elements with different affinities for the hnRNP H/H' protein influence the processing efficiency of mammalian polyadenylation signals.
    Nucleic Acids Res. 2002 Apr 15;30(8):1842-50 PMID: 11937639
  27. Reexamining the polyadenylation signal: were we wrong about AAUAAA?
    Mol Cell Endocrinol. 2002 Apr 25;190(1-2):1-8 PMID: 11997173
  28. Male germ cell gene expression.
    Recent Prog Horm Res. 2002;57:103-28 PMID: 12017539
  29. Long-range heterogeneity at the 3' ends of human mRNAs.
    Genome Res. 2002 Jul;12(7):1068-74 PMID: 12097343
  30. A history of poly A sequences: from formation to factors to function.
    Prog Nucleic Acid Res Mol Biol. 2002;71:285-389 PMID: 12102557
  31. Alternative splicing in the testes.
    Curr Opin Genet Dev. 2002 Oct;12(5):615-19 PMID: 12240623
  32. The gene CSTF2T, encoding the human variant CstF-64 polyadenylation protein tauCstF-64, lacks introns and may be associated with male sterility.
    Genomics. 2002 Nov;80(5):509-14 PMID: 12408968
  33. ARED 2.0: an update of AU-rich element mRNA database.
    Nucleic Acids Res. 2003 Jan 1;31(1):421-3 PMID: 12520039
  34. New microRNAs from mouse and human.
    RNA. 2003 Feb;9(2):175-9 PMID: 12554859
  35. Translational control by the 3'-UTR: the ends specify the means.
    Trends Biochem Sci. 2003 Feb;28(2):91-8 PMID: 12575997
  36. Downstream elements of mammalian pre-mRNA polyadenylation signals: primary, secondary and higher-order structures.
    Nucleic Acids Res. 2003 Mar 1;31(5):1375-86 PMID: 12595544
  37. Biased alternative polyadenylation in human tissues.
    Genome Biol. 2005;6(12):R100 PMID: 16356263
  38. Ensembl 2006.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D556-61 PMID: 16381931
  39. The Mouse Genome Database (MGD): updates and enhancements.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D562-7 PMID: 16381933
  40. Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice.
    Dev Cell. 2001 Aug;1(2):201-13 PMID: 11702780
  41. Regulation of mRNA translation by 5'- and 3'-UTR-binding factors.
    Trends Biochem Sci. 2003 Apr;28(4):182-8 PMID: 12713901
  42. Regulatory sequence analysis tools.
    Nucleic Acids Res. 2003 Jul 1;31(13):3593-6 PMID: 12824373
  43. Sequence determinants in human polyadenylation site selection.
    BMC Genomics. 2003 Feb 25;4(1):7 PMID: 12600277
  44. The power of the 3' UTR: translational control and development.
    Nat Rev Genet. 2003 Aug;4(8):626-37 PMID: 12897774
  45. A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets.
    Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12201-6 PMID: 14526100
  46. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  47. MicroRNA targets in Drosophila.
    Genome Biol. 2003;5(1):R1 PMID: 14709173
  48. Identification of conserved regulatory elements by comparative genome analysis.
    J Biol. 2003;2(2):13 PMID: 12760745
  49. Fast and effective prediction of microRNA/target duplexes.
    RNA. 2004 Oct;10(10):1507-17 PMID: 15383676
  50. 3' non-coding region sequences in eukaryotic messenger RNA.
    Nature. 1976 Sep 16;263(5574):211-4 PMID: 822353
  51. Identification of common molecular subsequences.
    J Mol Biol. 1981 Mar 25;147(1):195-7 PMID: 7265238
  52. Sequences capable of restoring poly(A) site function define two distinct downstream elements.
    EMBO J. 1986 Nov;5(11):2907-13 PMID: 3024967
  53. Position-dependent sequence elements downstream of AAUAAA are required for efficient rabbit beta-globin mRNA 3' end formation.
    Cell. 1987 May 8;49(3):399-406 PMID: 3568131
  54. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5311-5 PMID: 2440048
  55. Nucleotide sequence of testis-derived c-abl cDNAs: implications for testis-specific transcription and abl oncogene activation.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8200-4 PMID: 3317402
  56. Molecular characterization of the testis specific c-abl mRNA in mouse.
    EMBO J. 1987 Dec 20;6(13):4041-8 PMID: 3443101
  57. Subunits of cyclic adenosine 3',5'-monophosphate-dependent protein kinase show differential and distinct expression patterns during germ cell differentiation: alternative polyadenylation in germ cells gives rise to unique smaller-sized mRNA species.
    Biol Reprod. 1990 Jul;43(1):46-54 PMID: 2393692
  58. dbEST--database for "expressed sequence tags".
    Nat Genet. 1993 Aug;4(4):332-3 PMID: 8401577
  59. Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment.
    Science. 1993 Oct 8;262(5131):208-14 PMID: 8211139
  60. The 64-kilodalton subunit of the CstF polyadenylation factor binds to pre-mRNAs downstream of the cleavage site and influences cleavage site location.
    Mol Cell Biol. 1994 Oct;14(10):6647-54 PMID: 7935383
  61. The G-rich auxiliary downstream element has distinct sequence and position requirements and mediates efficient 3' end pre-mRNA processing through a trans-acting factor.
    Nucleic Acids Res. 1995 May 11;23(9):1625-31 PMID: 7784220
  62. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription.
    Nature. 1997 Jan 23;385(6614):357-61 PMID: 9002523
  63. Life and death in the cytoplasm: messages from the 3' end.
    Curr Opin Genet Dev. 1997 Apr;7(2):220-32 PMID: 9115434
  64. A comparison of mammalian and yeast pre-mRNA 3'-end processing.
    Curr Opin Cell Biol. 1997 Jun;9(3):329-36 PMID: 9159082
  65. Alternative poly(A) site selection in complex transcription units: means to an end?
    Nucleic Acids Res. 1997 Jul 1;25(13):2547-61 PMID: 9185563
  66. RNA recognition by the human polyadenylation factor CstF.
    Mol Cell Biol. 1997 Jul;17(7):3907-14 PMID: 9199325
  67. RNA ligands selected by cleavage stimulation factor contain distinct sequence motifs that function as downstream elements in 3'-end processing of pre-mRNA.
    J Biol Chem. 1997 Oct 17;272(42):26769-79 PMID: 9334264
  68. Mechanism and regulation of mRNA polyadenylation.
    Genes Dev. 1997 Nov 1;11(21):2755-66 PMID: 9353246
  69. Alternate polyadenylation in human mRNAs: a large-scale analysis by EST clustering.
    Genome Res. 1998 May;8(5):524-30 PMID: 9582195
  70. Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs.
    Nucleic Acids Res. 1998 Jun 15;26(12):2891-8 PMID: 9611233
  71. RNA polymerase II is an essential mRNA polyadenylation factor.
    Nature. 1998 Sep 3;395(6697):93-6 PMID: 9738505
  72. Highly conserved RNA sequences that are sensors of environmental stress.
    Mol Cell Biol. 1998 Dec;18(12):7371-82 PMID: 9819424
  73. Autoregulation at the level of mRNA 3' end formation of the suppressor of forked gene of Drosophila melanogaster is conserved in Drosophila virilis.
    Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14302-7 PMID: 9826695
  74. Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):405-45 PMID: 10357856
  75. Cytoplasmic polyadenylation in development and beyond.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):446-56 PMID: 10357857
  76. Specific transcriptional pausing activates polyadenylation in a coupled in vitro system.
    Mol Cell. 1999 May;3(5):593-600 PMID: 10360175
  77. Two distinct forms of the 64,000 Mr protein of the cleavage stimulation factor are expressed in mouse male germ cells.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6763-8 PMID: 10359786
  78. Construction and preliminary characterization of a series of mouse and rat testis cDNA libraries.
    J Androl. 1999 Sep-Oct;20(5):635-9 PMID: 10520576
  79. Human MicroRNA targets.
    PLoS Biol. 2004 Nov;2(11):e363 PMID: 15502875
  80. A large-scale analysis of mRNA polyadenylation of human and mouse genes.
    Nucleic Acids Res. 2005;33(1):201-12 PMID: 15647503
  81. Ontological visualization of protein-protein interactions.
    BMC Bioinformatics. 2005;6:29 PMID: 15707487
  82. Computational analysis of 3'-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat.
    Genome Res. 2005 Mar;15(3):369-75 PMID: 15741508
  83. Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals.
    Nature. 2005 Mar 17;434(7031):338-45 PMID: 15735639
  84. Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition.
    Genes Dev. 2005 Jun 1;19(11):1315-27 PMID: 15937220
  85. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
    Genome Res. 2005 Aug;15(8):1034-50 PMID: 16024819
  86. Mammalian sperm translate nuclear-encoded proteins by mitochondrial-type ribosomes.
    Genes Dev. 2006 Feb 15;20(4):411-6 PMID: 16449571
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl919
Published
2007-00-00
Epub
2006-00-08
Pages
234-46
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1802579
Subset
IM
Grants
NIGMS NIH HHS · GM072706 · United States
NICHD NIH HHS · R01 HD037102 · United States
NCRR NIH HHS · P20 RR016463 · United States
NICHD NIH HHS · R01 HD037109 · United States
NCRR NIH HHS · 2 P20 RR16463 · United States
NICHD NIH HHS · HD037102 · United States
NIGMS NIH HHS · R01 GM072706 · United States
External Links
PubMed source DOI: 10.1093/nar/gkl919 PMC Full Text View journal details
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